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Differential Mechanisms of Increased ₁-Fetoprotein Production in Rats following Carbon Tetrachloride Injury and Partial Hepatectomy¹

The First Department of Internal Medicine [A. W., K. T.] and Division of Pathology, Cancer Institute [M.M.], Okayama University Medical School, Okayama 700, Japan

² To whom inquiries and reprint requests should be addressed.

Possible differences in the mechanisms of increased ₁-fetoprotein (AFP) production following carbon tetrachloride (CCl₄) intoxication and partial hepatectomy were studied with 5-week-old rats at the time of sacrifice. The maximum level of serum AFP reached in 4 days after a single dose of CCl₄ was much higher than that after partial hepatectomy, although the incorporation of [³H]thymidine into liver DNA increased nearly to the same extent by either of these treatments. In the remnant after partial hepatectomy, the DNA synthesis that was further accelerated by treatment with a lower dose of thioacetamide was not associated with any further increase of serum AFP levels. However, CCl₄ given to partially hepatectomized rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl₄-injured rats were depressed by Mitomycin C given in vivo, whereas the increases in partially hepatectomized rats were not. Treatment with 8-azaguanine inhibited both increases of serum AFP levels, although the inhibition was much less or was insignificant in partially hepatectomized rats. These results suggest the existence of different underlying mechanisms of the increased AFP production for the two experimental conditions.

¹ A preliminary report on part of this work was presented at the Conference on Carcino-Fetal Proteins: Biology and Chemistry, Tokyo, November 1974. This constitutes Part II of a series entitled "Mechanisms of Increased ₁-Fetoprotein Production by Liver Injury."

Received 12/15/75. Accepted 3/19/76.